This application claims priority under 35 U.S.C. xc2xa7119 from Republic of Korea Patent Application Serial No. 34935/2000, filed Jun. 23, 2000, the disclosure of which is incorporated herein by reference in its entirety.
1. Field of the Invention
The present invention relates to a method for preparing biodegradable porous polymer scaffolds for tissue engineering, comprising:
a) fabricating sample from a polymer solution containing biodegradable polymer and effervescent mixture;
b) effervescing (foaming) the obtained polymer sample in the presence of an effervescent medium such as an aqueous alcohol solution; and
c) drying.
The present invention also relates to a biodegradable porous polymer scaffold for tissue engineering prepared by adopting the above method, which has a proper pore size, a high porosity and an open cell structure in which pores are interconnected.
2. Description of the Background Art
Tissue engineering which is one of the new fields opened with the development of the science and which is an applied study that utilize the basic concept and technique of life science and engineering gives a clue to understand co-relationship between a structure and a function of body tissue and make a substitute of the body tissue for transplantation, thereby to maintain, improve or restore the function of human body.
One of the typical tissue engineering techniques comprises taking out a required tissue from a patient body, followed by isolating cell from the tissue, proliferating the isolated cell, seeding the cell in the biodegradable porous polymer scaffolds, culturing the cell in vitro for a predetermined period, and then, transplanting the obtained hybrid-type cell/polymer structure into the human body. After transplantation is achieved, by virtue of diffusion of body fluids, oxygen and nutrients are provided to transplanted cells in biodegradable porous polymer until a blood vessel is newly formed. When a blood vessel is formed to which blood is supplied, the cells are cultivated and divided to form a new tissue and an organ. During new tissue and the organ form, the polymer scaffolds are degraded and disappear.
Accordingly, in the field of tissue engineering, it is important to prepare a biodegradable porous polymer scaffold that is similar to the body tissue.
In order to be used as a raw material of the polymer scaffolds, the material should serve as a matrix or a frame properly so that tissue cells can adhere to the surface of a material to form a tissue in a three-dimensional structure. It should also serve as a middle barrier positioned between a transplanted cell and a host cell. That is, it should be non-toxic and biocompatible such that neither blood coagulation nor inflammatory reaction occurs after transplantation.
In addition, it should be biodegradable such that as the transplanted cell functions properly as a tissue, it is completely degraded in vivo within a desired time.
Biodegradable polymers widely used as raw materials for the scaffold include polyglycolic acid (PGA), polylactic acid (PLA), lactic acid-glycolic acid copolymer (PLGA), poly-xcex5-caprolactone (PCL), polyamino acid, polyanhydride, polyorthoester, and copolymers thereof. However, to date, only PGA, PLA, and PLGA are approved as biodegradable polymers acceptable for use in human body by the U.S. FDA, and are being used as raw materials for biodegradable porous polymer scaffolds for regeneration within human body.
Meanwhile, recently, researchers have made various attempts to prepare polymer having a porous structure, for example, solvent-casting and particulate-leaching technique (A. G. Mikos, etc. Polymer, 35, 1068, 1994), wherein single crystal NaCl is mixed, dried and dissolved in water; gas forming technique (L. D. Harris, etc., Journal of Biomedical Materials Research, 42, 396, 1998), wherein polymer is inflated by using CO2 gas; fiber extrusion and fabric forming process (K. T. Paige, etc. Tissue Engineering, 1, 97, 1995), wherein polymer fiber is made to a nonwoven fabric to make a polymer mesh; thermally induced phase separation technique (C. Schugens, etc., Journal of Biomedical Materials Research, 30, 449, 1996), wherein solvent contained in the polymer solution is immersed in a nonsolvent to make porosity; and emulsion freeze-drying method (K. Whang, etc. Polymer, 36, 837, 1995), wherein polymer solution are mixed with water to make emulsion, which is then frozen with liquid nitrogen and freeze-dried.
However, with the conventional methods, it is not easy to control the size of the pores, porosity is comparatively low, and open structure is not formed well between pores. In addition, these methods have disadvantages in that the closed pore phenomenon occurs on the surface of the scaffolds, process is comparatively complicated, gas or toxic substance is secreted during the preparation of scaffolds, and salt remains in the scaffolds.
Therefore, an object of the present invention is to provide a new method that can substitute the solvent-casting and particulate-leaching technique and the gas forming technique that have been generally adopted to prepare a biodegradable porous polymer scaffold.
Another object of the present invention is to provide a novel method for preparing a biodegradable porous polymer scaffold for tissue engineering that can solve problems of the close pore phenomenon on the surface of the scaffolds, the complicate process, the secretion of toxic substance and the salt-remaining phenomenon.
Still another object of the present invention is to provide a novel method for preparing a biodegradable porous polymer scaffold in which the pore size is easily controlled.
Yet another object of the present invention is to provide biodegradable polymer scaffolds for tissue engineering that has high porosity and an open cell structure in which pores are interconnected with each other.
These and other objects described in the specification can be achieved by providing a method for preparing biodegradable porous polymer scaffolds, which comprises making a polymer sample from a polymer solution containing biodegradable polymer and effervescent mixture, effervescing (foaming) the polymer sample in the presence of an effervescent medium such as an aqueous alcohol solution, and drying, and biodegradable porous polymer scaffolds prepared by the method.